Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients With Advanced Kidney Cancer or Liver Cancer That Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborators:
Alliance for Clinical Trials in Oncology
Cancer and Leukemia Group B
American College of Surgeons
Threshold Pharmaceuticals
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier:
NCT01497444
First received: December 20, 2011
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as hypoxia-activated prodrug TH-302, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 may kill more tumor cells.

PURPOSE: This phase I/II trial studies the side effects and best dose of giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 and to see how well they work in treating patients with advanced kidney cancer or liver cancer that cannot be removed by surgery.


Condition Intervention Phase
Kidney Cancer
Liver Cancer
Drug: hypoxia-activated prodrug TH-302
Drug: sorafenib tosylate
Genetic: protein analysis
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Sorafenib + TH-302: Phase I in Advanced Renal Cell Carcinoma (RCC) and Advanced Hepatocellular Carcinoma (HCC) and Phase II in 1st Line Advanced HCC

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Number of dose-limiting toxicity incidents as assessed by CTCAE version 4.0 (Phase I) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
  • MTD of sorafenib tosylate and TH-302 (Phase I) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Overall response rate (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events as assessed by NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Overall response rate based on standard RECIST criteria (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Duration of response based on modified (standard) RECIST criteria (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • PFS (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • OS (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • AFP response rate (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: May 2012
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sorafenib and TH-302
Patients will be administered sorafenib tablets to take twice daily by mouth, every day of each cycle. Patients will also be given TH-302 intravenously (IV) on days 8, 15 and 22 of each cycle. A cycle is 28 days.
Drug: hypoxia-activated prodrug TH-302 Drug: sorafenib tosylate Genetic: protein analysis Other: laboratory biomarker analysis

Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum-tolerated dose (MTD) and recommended Phase II dosing (RP2D) for the combination of sorafenib tosylate and hypoxia-activated prodrug TH-302 (TH-302) in patients with hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC; non-HCC) advanced solid tumors. (Phase I)
  • To evaluate the overall response rate (RR) determined based on modified RECIST criteria (Lencioni and Llovet 2010) in patients with advanced HCC receiving sorafenib tosylate with TH-302. (Phase II)

Secondary

  • To characterize overall toxicity profile of sorafenib tosylate + TH-302 within patients with HCC and RCC (non-HCC) advanced solid tumors. (Phase I)
  • To characterize the responses of sorafenib tosylate + TH-302 within patients with HCC and RCC (non-HCC) advanced solid tumors. (Phase I)
  • To assess the adverse events (AEs) profile and safety profile of sorafenib tosylate in combination with TH-302 in patients with advanced HCC. (Phase II)
  • To estimate the overall response rate based on standard RECIST criteria in the study population. (Phase II)
  • To estimate the duration of response based on modified (standard) RECIST criteria in the study population. (Phase II)
  • To estimate the progression free survival (PFS) in the study population. (Phase II)
  • To estimate the overall survival (OS) in the study population. (Phase II)
  • To estimate the alpha-fetoprotein (AFP) response rate (defined as > 20% decrease of AFP from baseline) in the study population. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.

Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28 and hypoxia-activated prodrug TH-302 IV over 30 minutes on days 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection periodically during study for alpha-fetoprotein analysis.

After completion of study treatment, patients are followed up for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Cytologically or histologically confirmed diagnosis of advanced hepatocellular carcinoma (HCC) or renal cell carcinoma; HCC patients should not be amenable to treatment with surgery or to orthotopic liver transplant (phase I)
  • Cytologically or histologically confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic and is not amenable to treatment with surgery or to orthotopic liver transplant (phase II)
  • Patients must have measurable disease
  • HCC patients only:

    • Advanced HCC after first-line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib tosylate therapy only) treatment (phase I)
    • Advanced HCC after first-line treatment (i.e., no prior systemic therapy) (phase II)
    • Child Pugh class A or B7 liver disease
    • Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if ≥ 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable
  • No known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated

    • Patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis
    • Patients with CNS metastases that have been treated and are stable without symptoms for ≥ 4 weeks after completion of treatment are eligible
  • HCC patients only: cancer potentially amenable to local modalities of therapy or surgical resection not allowed
  • No fibrolamellar histology HCC, mixed hepatocholangiocarcinoma, hepatic sarcomas, and other non-HCC primary liver tumors

PATIENT CHARACTERISTICS:

  • ECOG performance status 0 or 1
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1,200/mm³
  • Peripheral platelet count ≥ 75,000/mm³
  • Hemoglobin > 8.5 g/dL
  • Total bilirubin ≤ 3.0 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (if patient has HCC or liver metastases, then ≤ 5 times ULN) (phase I)
  • Creatinine ≤ 1.5 times ULN
  • International normalized ratio (INR) ≤ 1.5 times ULN
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
  • Willing to return to North Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
  • Ability to receive intravenous contrast for the purpose of imaging (phase II)
  • None of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception for the duration of study participation; men and women should continue to use adequate birth control after the last administration of sorafenib tosylate and hypoxia-activated prodrug TH-302 (TH-302) under the guidance of their treating physician
  • No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No other active malignancy ≤ 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • No inadequately controlled hypertension (systolic blood pressure of > 150 mm Hg or diastolic pressure > 100 mm Hg on anti-hypertensive medications)
  • No New York Heart Association (NYHA) classification III or IV congestive heart failure
  • No known or suspected allergy or hypersensitivity to any component of TH-302, sorafenib tosylate, or any of the sorafenib tosylate excipients
  • No condition that severely impairs patient's ability to swallow whole pills
  • No QTc interval > 500 msec on baseline electrocardiogram (EKG)
  • No documented history of prolonged QTc interval ≤ 6 months prior to registration
  • No traumatic injury in the past 14 days

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Not receiving any other investigational agent
  • No major surgical procedures prior to registration or anticipation of need for elective or planned major surgical procedure during the course of the study
  • No treatment with radiation therapy or investigational therapy ≤ 28 days prior to registration
  • RCC patients only: No chemotherapy prior to study entry within 5 half-lives of the agent (as described in the package insert), or 4 weeks prior to registration (whichever is shorter) with resolution of side effects from therapy to ≤ grade 1
  • No medication that has documented data or is generally accepted as having increased risk of QT prolongation and/or Torsades de Pointes
  • Not receiving any medications or substances that are inducers or strong or moderate inhibitors of CYP3A4 ≤ 7 days prior to registration
  • Patients receiving anti-coagulation therapy are permitted as long as they have a stable INR ≤ 3.0
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01497444

Locations
United States, Arizona
Mayo Clinic Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
Sponsors and Collaborators
North Central Cancer Treatment Group
Alliance for Clinical Trials in Oncology
Cancer and Leukemia Group B
American College of Surgeons
Threshold Pharmaceuticals
Investigators
Principal Investigator: Mitesh J. Borad, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier: NCT01497444     History of Changes
Other Study ID Numbers: N1153, NCCTG-N1153, CDR0000720022, NCI-2012-00095, U10CA031946
Study First Received: December 20, 2011
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
recurrent adult primary liver cancer
recurrent renal cell cancer
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Sorafenib
Phosphoramide Mustards
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 28, 2014